Respiratory intermediate care units: a European survey.
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Data Collection↗
Biomedical subjects
M Confalonieri
Publications and source records attributed to M Confalonieri.
Where to perform noninvasive ventilation?
Noninvasive positive-pressure ventilation (NPPV) has been shown to be a means of reducing the need for endotracheal intubation, which when effective reduces the complication rate and improves outcome. Because paralysis and sedation are not needed and because the patient is not necessarily dependent upon a machine for respiration, ventilation outside the intensive care unit (ICU) is an option. A number of studies have shown that NPPV for acute exacerbations of chronic obstructive pulmonary disease (COPD) can be effective in the non-ICU environment, though usually in patients with less severe exacerbations. However, there have been no direct comparisons of the application of NPPV in different locations. The likelihood of success of the technique is an important factor in deciding there NPPV should be performed. Ready access to invasive ventilation is important when NPPV is not indicated from the outset or fails after an initial trial. In acute exacerbations of COPD, NPPV is less likely to be successful the more severe the exacerbation, as measured by the severity of acidosis. Good tolerance of NPPV, which translates into an improvement in pH and a fall in respiratory rate, predicts a successful outcome and is a useful way of monitoring progress. NPPV has been shown to be cost effective both in the ICU and when performed on general wards. A dedicated intermediate care unit with particular expertise in noninvasive modes of ventilation may provide the best environment, both in terms of outcome, but also cost effectiveness. The ideal location for noninvasive positive-pressure ventilation will vary from country to country and indeed from hospital to hospital, depending upon local factors. However, the most important factor is that staff be adequately trained in the technique and be available throughout the 24-h period.
Emergency Medical Services↗
Predictors of failure of noninvasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: a multi-center study.
CONTEXT: In patients with hypoxemic acute respiratory failure (ARF), randomized studies have shown noninvasive positive pressure ventilation (NPPV) to be associated with lower rates of endotracheal intubation. In these patients, predictors of NPPV failure are not well characterized. OBJECTIVE: To investigate variables predictive of NPPV failure in patients with hypoxemic ARF. DESIGN: Prospective, multicenter cohort study. SETTING: Eight Intensive Care Units (ICU) in Europe and USA. PATIENTS: Of 5,847 patients admitted between October 1996 and December 1998, 2,770 met criteria for hypoxemic ARF. Of these, 2,416 were already intubated and 354 were eligible for the study. RESULTS: NPPV failed in 30% (108/354) of patients. The highest intubation rate was observed in patients with ARDS (51%) or community-acquired pneumonia (50%). The lowest intubation rate was observed in patients with cardiogenic pulmonary edema (10%) and pulmonary contusion (18%). Multivariate analysis identified age > 40 years (OR 1.72, 95% CI 0.92-3.23), a simplified acute physiologic score (SAPS II) > or = 35 (OR 1.81, 95% CI 1.07-3.06), the presence of ARDS or community-acquired pneumonia (OR 3.75, 95% CI 2.25-6.24), and a PaO2:FiO2 < or = 146 after 1 h of NPPV (OR 2.51, 95% CI 1.45-4.35) as factors independently associated with failure of NPPV. Patients requiring intubation had a longer duration of ICU stay ( P < 0.001), higher rates of ventilator-associated pneumonia and septic complications ( P < 0.001), and a higher ICU mortality ( P < 0.001). CONCLUSIONS: In hypoxemic ARF, NPPV can be successful in selected populations. When patients have a higher severity score, an older age, ARDS or pneumonia, or fail to improve after 1 h of treatment, the risk of failure is higher.
Acute Disease↗
Clinical relevance of monitoring respiratory mechanics in the ventilator-supported patient: an update (1995-2000).
The introduction of mechanical ventilation in the intensive care unit environment had the merit of putting a potent life-saving tool in the physicians' hands in a number of situations; however, like most sophisticated technologies, it can cause severe side effects and eventually increase mortality if improperly applied. Assessment of respiratory mechanics serves as an aid in understanding the patient-ventilator interactions with the aim to obtain a better performance of the existing ventilator modalities. It has also provided a better understanding of patients' pathophysiology. Thanks to it, new ventilatory strategies and modalities have been developed. Finally, on-line monitoring of respiratory mechanics parameters is going to be more than a future perspective.
Adult↗
Respiratory intensive care units in Italy: a national census and prospective cohort study.
BACKGROUND: In Italy, respiratory intensive care units (RICUs) provide an intermediate level of care between the intensive care unit (ICU) and the general ward for patients with single organ respiratory failure. Because of the lack of official epidemiological data in these units, a two phase study was performed with the aim of describing the work profile in Italian RICUs. METHODS: A national survey of RICUs was conducted from January to March 1997 using a questionnaire which comprised over 30 items regarding location, models of service provision, staff, and equipment. The following criteria were necessary for inclusion of a unit in the survey: (1) a nurse to patient ratio ranging from 1:2.5 to 1:4 per shift; (2) availability of adequate continuous non-invasive monitoring; (3) expertise for non-invasive ventilation (NIV) and for intubation in case of NIV failure; (4) physician availability 24 hours a day. Between November 1997 and January 1998 a 3 month prospective cohort study was performed to survey the patient population admitted to the RICUs. RESULTS: Twenty six RICUs were included in the study: four were located in rehabilitation centres and 22 in general hospitals. In most, the reported nurse to patient ratio ranged from 1:2 to 1:3, with 36% of units reporting a ratio of 1:4 per shift. During the study period 756 consecutive patients of mean (SD) age 68 (12) years were admitted to the 26 RICUs. The highest proportion (47%) were admitted from emergency departments, 19% from other medical wards, 18% were transferred from the ICU, 13% from specialist respiratory wards, and 2% were transferred following surgery. All but 32 had respiratory failure on admission. The reasons for admission to the RICU were: monitoring for expected clinical instability (n=221), mechanical ventilation (n=473), and weaning (n=59); 586 patients needed mechanical ventilation during their stay in the RICU, 425 were treated with non-invasive techniques as a first line of treatment (374 by non-invasive positive pressure, 51 by iron lung), and 161 underwent invasive mechanical ventilation (63 intubated, 98 tracheostomies). All but 48 patients had chronic respiratory disease, mainly chronic obstructive pulmonary disease (COPD; n=451). More than 70% of patients (n=228) had comorbidity, mainly consisting of heart disorders. The median APACHE II score was 18 (range 1--43). The predicted inpatient mortality risk rate according to the APACHE II equation was 22.1% while the actual inpatient mortality rate was 16%. The mean length of stay in the RICU was 12 (11) days. The outcome in most patients (79.2%) admitted to RICUs was favourable. CONCLUSIONS: Italian RICUs are specialised units mainly devoted to the monitoring and treatment of acute on chronic respiratory failure by non-invasive ventilation, but also to weaning from invasive mechanical ventilation. The results of this study provide a useful insight into an increasingly important field of respiratory medicine.
APACHE↗
Respiratory intermediate (high dependency) unit care in Europe: models of service provision.
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Critical Care↗
Burden of chronic obstructive pulmonary disease.
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Adult↗
Microbiological confirmation of tuberculosis cases at diagnosis and at the end of treatment in Italy.
Microbiological findings at diagnosis and at the end of treatment are relevant for evaluating tuberculosis (TB) treatment programmes. The objectives of this study were to describe the microbiological findings at diagnosis and at the end of treatment in pulmonary and extrapulmonary TB patients treated under programme conditions in Italy. The study was a prospective monitoring activity based on the collection of standard recording and reporting forms from a representative sample of Italian TB Units. The forms with individual data were reviewed and analysed on a quarterly basis, 9 months after enrolment. The complete bacteriological profile of patients was analysed at diagnosis and at the completion of treatment. Individual data on 992 patients were analysed. At diagnosis 320 (32.2%) of cases were pulmonary sputum smear positive, 361 (36.4%) pulmonary smear negative or not done and 311 (33.4%) extrapulmonary; 424 (42.7%) of all TB cases were culture confirmed at diagnosis (368, 50.2%, of pulmonary cases); 575 (84.4%) of pulmonary cases had a culture done at diagnosis and 156 (22.9%) at the end of treatment (p < 0.001); 572 (84%) had a sputum smear done at diagnosis and 164 (24.1%) at the end of treatment (p < 0.001). Although the rate of bacteriologically confirmed cases is similar to that of other European countries, the bacteriological confirmation at diagnosis and, particularly, at the end of treatment, is sub-optimal. The importance of further disseminating national guidelines among physicians managing TB is emphasized, in order to achieve a higher proportion of TB cases bacteriologically confirmed at diagnosis and monitored at the end of treatment.
Antitubercular Agents↗
Induced sputum cellularity. Reference values and distribution in normal volunteers.
Sputum induction has recently been proposed as the only direct noninvasive method for measuring airway inflammatory indices. The reference values and the distribution of cells in induced sputum in a control population have not yet been well defined. We therefore evaluated data from a large number of healthy volunteers. One hundred fourteen healthy, nonatopic, nonsmoking volunteers without airway hyperreactivity were enrolled (age: 38 +/- 13 yr [mean +/- SD]; FEV(1): 105 +/- 10% predicted; provocative dose of methacholine inducing a 20% decrease FEV(1) > 3,200 microgram). Ninety-six subjects (84%) produced adequate analysis samples. The subjects had a normal age distribution. Their induced sputum was rich in macrophages (69.2 +/- 13%) and neutrophils (27.3 +/- 13%), and poor in eosinophils (0.6 +/- 0.8%), lymphocytes (1.0 +/- 1.2%), and epithelial cells (1.5 +/- 1.8%). Only macrophages and neutrophils showed a normal distribution; total and differential counts of other cells did not. We propose that these data be used in comparison of the induced sputum cells of normal subjects and those of patients with airway inflammation.
Adult↗
The appropriate setting of noninvasive pressure support ventilation in stable COPD patients.
STUDY OBJECTIVE: To evaluate the short-term physiologic effects of two settings of nasal pressure-support ventilation (NPSV) in stable COPD patients with chronic hypercapnia. DESIGN: Randomized controlled physiologic study. SETTING: Lung function units and outpatient clinic of two affiliated pulmonary rehabilitation centers. PATIENTS: Twenty-three patients receiving domiciliary nocturnal NPSV for a mean (+/- SD) duration of 31 +/- 20 months. METHODS: Evaluation of arterial blood gases, breathing pattern, respiratory muscles, and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn) during both unassisted and assisted ventilation. Two settings of NPSV were randomly applied for 30 min each: (1) usual setting (U), the setting of NPSV actually used by the individual patient at home; and (2) physiologic setting (PHY), the level of inspiratory pressure support (IPS) and external positive end-expiratory pressure (PEEPe) tailored to patient according to invasive evaluation of respiratory muscular function and mechanics. RESULTS: All patients tolerated NPSV well throughout the procedure. Mean U was IPS, 16 +/- 3 cm H(2)O and PEEPe, 3.6 +/- 1.4 cm H(2)O; mean PHY was IPS, 15 +/- 3 cm H(2)O and PEEPe, 3.1 +/- 1.6 cm H(2)O. NPSV was able to significantly (p < 0.01) improve arterial blood gases independent of the setting applied. When compared with spontaneous breathing, both settings induced a significant increase in minute ventilation (p < 0.01). Both settings were able to reduce the diaphragmatic pressure-time product, but the reduction was significantly greater with PHY (by 64%; p < 0.01) than with U (56%; p < 0.05). Eleven of 23 patients (48%) with U and 7 of 23 patients (30%) with PHY showed ineffective efforts (IE); the prevalence of IE (20 +/- 39% vs 6 +/- 11% of their respiratory rate with U and PHY, respectively) was statistically different (p < 0.05). CONCLUSION: In COPD patients with chronic hypercapnia, NPSV is effective in improving arterial blood gases and in unloading inspiratory muscles independent of whether it is set on the basis of patient comfort and improvement in arterial blood gases or tailored to a patient's respiratory muscle effort and mechanics. However, setting of inspiratory assistance and PEEPe by the invasive evaluation of lung mechanics and respiratory muscle function may result in reduction in ineffective inspiratory efforts. These short-term results must be confirmed in the long-term clinical setting.
Aged↗
[Surgical treatment of varicocele with inguinal microligation technique. 6-year experience].
BACKGROUND: Varicocele is found approximately in 15% of the male population and is considered a major cause of infertility. Varicocele management include surgical (traditional or laparoscopic) or conservative techniques (sclerotherapy). The authors present their experience on microsurgical inguinal varicocelectomy. This technique has been adopted since 1992 to decrease the incidence of recidives of high spermatic vein ligation; it also permitted to use local or loco-regional anesthesia, reducing time of hospitalization and realizing a minimally invasive approach. METHODS: From 1992 to 1997, 433 microsurgical inguinal varicocelectomy with artery and lymphatic sparing have been performed at the Militar Hospital of Milan in 409 young men with idiopathic varicocele. All patients were discharged 24 hours after operation. Only those who lived particularly far from the hospital remained for 48 hours. RESULTS: Clinical controls were performed I, III, VI months after operation. At the third control (VI month), a new semen analysis was performed, and 65% of patients had an improvement of seminal characteristics. In 394 patients, a complete resolution of varicocele was observed; 4 patients had a recurrence of the pathology and 11 had a recidive. Seventy-three patients who presented a concomitant homolateral inguinal hernia were treated at the same time. CONCLUSIONS: The conclusion is drawn that microsurgical ligation of spermatic veins represents a good surgical option in the treatment of varicocele. It is a quite simple technique that guarantees a low risk of recidives, permits using local or loco-regional anesthesia and can be performed in day-surgery with good results, few complications and good short and long term results.
Adolescent↗
Patient-ventilator asynchrony during noninvasive ventilation: the role of expiratory trigger.
OBJECTIVE: Air leaks around the mask are very likely to occur during noninvasive ventilation, in particular when prolonged ventilatory treatment is required. It has been suggested that leaks from the mask may impair the expiratory trigger cycling mechanism when inspiratory pressure support ventilation (PSV) is used. The aim of this study was to compare the short-term effect of two different expiratory cycling mechanisms (time-cycled vs flow-cycled) during noninvasive inspiratory pressure support ventilation (NIPSV) on patient-ventilator synchronisation in severe hypoxemic respiratory failure. STUDY POPULATION: Six patients with acute lung injury (ALI) due to acquired immunodeficiency syndrome (AIDS)-related opportunistic pneumonia were enrolled in the protocol. INTERVENTION: Each subject was first studied during spontaneous breathing with a Venturi oxygen mask (SB) and successively submitted to a randomly assigned 20' conventional flow-cycling (NIPSVfc) or time-cycling inspiratory pressure support ventilation (NIPSVtc). The pre-set parameters were: inspiratory pressure of 10 cm H2O, PEEP of 5 cm H2O for the same inspired oxygen fraction as during SB. A tight fit of the mask was avoided in order to facilitate air leaks around the mask. The esophageal pressure time product (PTPes) and tidal swings (delta Pes) were measured to evaluate the patient's respiratory effort. A subjective "comfort score" and the difference between patient and machine respiratory rate [delta RR(p-v)], calculated on esophageal and airway pressure curves, were used as indices of patient-machine interaction. RESULTS: Air leaks through the mask occurred in five out of six patients. The values of PEEPi (< 1.9 cm H2O) excluded significant expiratory muscle activity. NIPSVtc significantly reduced PTPes, delta Pes, and delta RR(p-v) when compared to NIPS-Vfc [230 +/- 41 (SE) vs 376 +/- 72 cm H2O.s.min-1; 8 +/- 2 vs 13 +/- 2 cm H2O; 1 +/- 1 vs 9 +/- 2 br.min-1; respectively] with a concomitant significant improvement of the "comfort score". CONCLUSIONS: In the presence of air leaks a time-cycled expiratory trigger provides a better patient-machine interaction than a flow-cycled expiratory trigger during NIPSV.
AIDS-Related Opportunistic Infections↗
Effect of methacholine challenge on cellular composition of sputum induction.
BACKGROUND: Induced sputum and methacholine inhalation challenge are routinely used for the assessment of airway inflammation and airway hyperresponsiveness, respectively. This study investigates whether a methacholine challenge performed one hour before sputum induction alters the cellular and biochemical constituents of sputum. METHODS: Sixteen stable asthmatic patients with lung function within the normal range underwent two sputum inductions within one week. One hour before one of the sputum inductions a methacholine challenge was performed. RESULTS: There were no significant differences in total cell count, macrophages, neutrophils, eosinophils, lymphocytes, epithelial cells, ECP, and albumin between the two challenges. The repeatability of cell counts was good for all cells, ECP and albumin, but poor for total cells. CONCLUSIONS: In patients with stable asthma a methacholine challenge carried out one hour before sputum induction does not significantly alter the cellular and biochemical constituents of sputum.
Adolescent↗
Acute respiratory failure in patients with severe community-acquired pneumonia. A prospective randomized evaluation of noninvasive ventilation.
In uncontrolled studies, noninvasive positive pressure ventilation (NPPV) was found useful in avoiding endotracheal intubation in patients with acute respiratory failure (ARF) caused by severe community-acquired pneumonia (CAP). We conducted a prospective, randomized study comparing standard treatment plus NPPV delivered through a face mask to standard treatment alone in patients with severe CAP and ARF. Patients fitting the American Thoracic Society criteria for severe CAP were included in presence of ARF (refractory hypoxemia and/or hypercapnia with acidosis). Exclusion criteria were: severe hemodynamic instability, requirement for emergent cardiopulmonary resuscitation, home mechanical ventilation or oxygen long-term supplementation, concomitant severe disease with a low expectation of life, inability to expectorate or contraindications to the use of the mask. Fifty-six consecutive patients (28 in each arm) were enrolled, and the two groups were similar at study entry. The use of NPPV was well tolerated, safe, and associated with a significant reduction in respiratory rate, need for endotracheal intubation (21% versus 50%; p = 0.03), and duration of intensive care unit (ICU) stay (1.8 +/- 0.7 d versus 6 +/- 1.8 d; p = 0.04). The two groups had a similar intensity of nursing care workload, time interval from study entry to endotracheal intubation, duration of hospitalization, and hospital mortality. Among patients with chronic obstructive pulmonary disease (COPD), those randomized to NPPV had a lower intensity of nursing care workload (p = 0.04) and improved 2-mo survival (88.9% versus 37.5%; p = 0.05). We conclude that in selected patients with ARF caused by severe CAP, NPPV was associated with a significant reduction in the rate of endotracheal intubation and duration of ICU stay. A 2-mo survival advantage was seen in patients with COPD.
Acute Disease↗
Gas exchange response to exercise in patients with chronic heart failure.
The objective of the study was investigate the pulmonary gas exchange response to exercise in 16 male patients with chronic heart failure (CHF) due to previous myocardial infarction and left ventricular dysfunction (ejection fraction < 45%). All patients underwent a symptom-limited exercise test during which cardiac frequency (fC), tidal volume (VT), respiratory frequency (fR), minute ventilation (V'E), oxygen consumption (V'O2) and carbon dioxide production (V'CO2) were measured on a breath-by-breath basis. Ventilatory equivalent for carbon dioxide (V'E/V'CO2) and lactate threshold (LT) were calculated. Arterial blood gas levels were measured at rest and at peak exercise. The dead space (VD) to tidal volume ratio (VD/VT) and alveolar-arterial oxygen gradient (PA-a,O2) were computed. Two subgroups of patients were identified according to peak V'O2 (V'O2,peak), group A (n = 7), V'O2,peak > 14 mL.kg-1.min-1 (17.2 +/- 2.5 SEM, range 14.5-20.8), and group B (n = 9), V'O2,peak < 14 mL.kg-1.min-1 (11.9 +/- 1.8, range 9.2-13.6). Arterial oxygen tension (Pa,O2) increased from rest to peak exercise in both groups (group A: 12.2 +/- 0.94 to 13.4 +/- 0.82 kPa (91.4 +/- 7.1 to 100.4 +/- 6.2 mmHg), p < 0.05; group B: 11.7 +/- 1.0 to 13.4 +/- 1.1 kPa (88.0 +/- 7.8 to 100.9 +/- 8.2 mmHg), p < 0.01), while a significant reduction in arterial carbon dioxide tension (Pa,CO2), from rest to peak exercise, was observed in group B only (4.64 +/- 0.39 to 4.08 +/- 0.36 kPa (34.9 +/- 2.8 to 30.7 +/- 2.7 mmHg), p < 0.005). Maximal V'E and maximal power (Powermax) were significantly lower in group B compared to group A (V'E 37.6 +/- 8.4 versus 52.1 +/- 13.8 L.min-1, p < 0.05; Powermax 64.4 +/- 12 versus 82.8 +/- 14.1 W, p < 0.01). fC was not significantly different at peak exercise, although the work load was significantly higher in group A. VD/VT failed to decrease significantly at maximal exercise in both groups. In group B, V'E/V'CO2 tended to be higher than in group A. In chronic heart failure patients, measurements of arterial blood gas levels during exercise might help to identify those subjects with a more pronounced depression of left ventricular function. At peak exercise, high ventilatory demand and respiratory alkalosis were observed in group B patients, suggesting an increased responsiveness of the respiratory centre that might be one major factor contributing to this excessive ventilatory response to exercise; vice versa, a combination of ventilation-perfusion mismatch, wasted ventilation and unpaired peripheral blood circulation seem to play only a minor role.
Aged↗
Respiratory high-dependency care units in Italy.
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Humans↗
Haemodynamic response during initiation of non-invasive positive pressure ventilation in COPD patients with acute ventilatory failure.
The aim of this study was to check non-invasively the acute haemodynamic effects of non-invasive positive pressure ventilation (NPPV) initiation in patients with chronic obstructive pulmonary disease (COPD) and acute ventilatory failure (AVF). Nineteen consecutive COPD patients with AVF were evaluated clinically and echocardiographically during spontaneous breathing with O2 supplementation and during NPPV plus O2. NPPV was administered with a scheduled inspiratory pressure of 15 cmH2O and an expiratory pressure of 4 cmH2O, via facial mask. Arterial blood gas improved significantly (pH and PaCO2; P < 0.001) during NPPV administration in all patients; none had hypotension or acute arrhythmia. Doppler echocardiographic evaluation was feasible in most of the patients (16/18). With reference to baseline values, no significant changes in pulmonary artery pressures and cardiac output (CO) were observed by Doppler echocardiography in most patients. Only four patients (21%) showed a significant reduction (> 15%) of CO during NPPV. No correlation was found between decreased CO and baseline data, but three patients showing CO reduction had poor tolerance to mask ventilation and did not improve respiratory rate during NPPV. It was concluded that the initiation of NPPV by facial mask does not alter haemodynamics acutely in most COPD patients with AVF, but individual patients may experience reduction in CO in spite of adequate oxygen saturation levels. This suggests that caution should be used when applying pre-determined and fixed pressures during NPPV. Monitoring haemodynamics by Doppler echocardiography may be useful for early detection of haemodynamic alterations due to NPPV application in patients with AVF.
Aged↗
Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease.
BACKGROUND: Airways inflammation is a feature of chronic obstructive pulmonary disease (COPD), but the role of corticosteroids in the management of clinically stable patients has yet to be established. A randomised controlled study was carried out to investigate the effect of high dose inhaled beclomethasone dipropionate (BDP) administered for two months to patients with stable, smoking related COPD. Sputum induction was used to evaluate bronchial inflammation response. METHODS: 34 patients (20 men and 14 women) were examined on three separate occasions. At the initial clinical assessment (visit 0), spirometry and blood gas analysis were performed. On visit 1 (within one week of visit 0) sputum induction was performed and each patient was randomised to receive either BDP 500 micrograms three times daily (treated group) or nothing (control group). After two months (visit 2), all patients underwent repeat clinical assessment, spirometry, and sputum induction. RESULTS: There were no differences in sputum cell counts between the groups at baseline. After two months of treatment, induced sputum samples from patients in the treated group showed a reduction in both neutrophils (-27%) and total cells (-42%) with respect to baseline, while the control group did not (neutrophils +9%, total cells +7%). Macrophages increased in the treated group but not in the control group. The mean final value of sputum neutrophils was 52% in the treated group and 73.3% in the control group (95% confidence interval (CI) -27.2 to -15.4). The mean final value of sputum macrophages was 35.8% in treated group and 19.3% in control group (95% CI 10.3 to 22.8). The differences between the treated and control groups for neutrophils (-21.3%), macrophages (+16.5%), and total cells (-65%) were significant. Spirometry and blood gas data did not change from baseline in either patient group. CONCLUSIONS: A two month course of treatment with high dose inhaled BDP reduces significantly neutrophil cell counts in patients with clinically stable, smoking related COPD. Further studies on the effectiveness of inhaled steroids in COPD are needed to confirm the clinical importance of this observation.
Administration, Inhalation↗